1. Field Of The Invention
The invention relates to new processes for the production of 4-hydroxy-2-oxopyrrolidin-1-yl-acetamide of formula: ##STR2## as well as to 4-(C.sub.1 -C.sub.4)-alkoxy-3-pyrrolin-2-on-1-yl-acetic acids as new intermediate products.
2. Background Art
4-Hydroxy-2-oxopyrrolidin-1-yl-acetamide is a cerebrally active pharmaceutical agent, which is known under the name oxiracetam [Pifferi et al., Il Farmaco, Ed. Sc., (1977), 32, page 6023. Numerous syntheses are known for producing such active ingredient.
Thus, from European Published Patent Application No. 224256, it is known to react a 4-halo-3-(C.sub.1 -C.sub.2)-alkoxy-2E-butenoic acid-C.sub.1-C.sub.4 alkyl ester with a glycine ester to the corresponding 4-(C.sub.1 -C.sub.2)-alkoxy-3-pyrrolin-2-on-1-yl-acetic acid alkyl ester. From Swiss Patent No. 668066, it is known to hydrogenate this ester with the help of a palladium catalyst with hydrogen, then to remove the alkoxy groups with trichloromethylsilane and sodium iodide and to react the resultant 4-hydroxy-2-oxopyrrolidine acetate with ammonia to provide the end product. From European Patent Appln. No. 216325, it is further known to hydrolyze the alkoxy group in a 4-(C.sub.1 -C.sub.2)-alkoxy-3-pyrrolin-2-on-1-yl acetic acid alkyl ester, to hydrogenate the resultant 2,4-dioxopyrrolidin-1-yl-acetic acid alkyl ester with sodium borohydride and to react the formed 4-hydroxy-2-oxo-pyrrolidin-1-yl acetate finally with ammonia to provide the end product. The known syntheses have the drawback that undesirable 2-oxopyrrolidin-1-yl-acetic acid derivatives occur, particularly in the hydrogenation step, in considerable amounts, which can be separated from the respective reaction mixture only with much difficulty and at great expense.
From an ecological viewpoint, the reaction with glycine ester, known according to European Patent Appln. No. 224256, has additionally the drawback that the reaction necessarily has to be performed in organic solvents to achieve a satisfactory result.